1. Field of the Invention
This invention relates to a dry reagent strip that measures blood glucose concentration; more particularly, a strip that makes the glucose measurement without requiring a meter.
2. Description of the Related Art
Many visual test devices have been developed for measuring the concentration of certain analytes in biological fluids. These devices have, for example, measured glucose, cholesterol, proteins, ketones, phenylalanine, or enzymes in blood, urine, or saliva.
Among the devices that are in most widespread use today is the blood glucose monitor. In the U.S. alone, there are estimated to be more than 14 million people with diabetes. In order to avoid serious medical problems, such as vision loss, circulatory problems, kidney failure, etc., many of these people monitor their blood glucose on a regular basis and then take the steps necessary to maintain their glucose concentration in an acceptable range.
Reagent strips, that are used in these devices contain an indicator which turns a different shade of color, depending on the concentration of glucose in the whole blood sample that has been applied to the strip. Although some of these strips use reduction chemistries, more commonly they involve an oxidizable dye or dye couple. Some of the strips include an enzyme, such as glucose oxidase, which is capable of oxidizing glucose to gluconic acid and hydrogen peroxide. They also contain an oxidizable dye and a substance having peroxidative activity, which is capable of selectively catalyzing oxidation of the oxidizable dye in the presence of hydrogen peroxide.
U.S. Pat. No. 3,298,789, issued Jan. 17, 1967 to R. L. Mast, discloses a bibulous paper strip that incorporates a reagent composition which changes color when glucose-containing blood is applied to its surface. In use, the blood is wiped off one minute after being applied to the surface, and the color of the strip is compared with a color chart having color blocks representing specific glucose levels.
U.S. Pat. No. 3,630,957, issued Dec. 28, 1971 to H. Rey et al., discloses a plastic foil strip that is coated with a reagent composition. The process of use is similar to that disclosed in the earlier patentxe2x80x94apply blood, wait about a minute, compare the resultant color with a color chart.
U.S. Pat. No. 4,975,367, issued Dec. 4, 1990 to Albarella et al., discloses a color-match strip that is designed to provide different hues at different analyte concentrations, by using two independent indicator systems. It also discloses the option of including a color retardant to delay the catalytic effect of the independent systems, changing the final hue produced for a particular concentration of analyte.
U.S. Pat. No. 5,200,325, issued Apr. 6, 1993 to J. M. Blatt et al., discloses a xe2x80x9cself-indicatingxe2x80x9d strip, in which color-chart comparisons are not required. The strip indicates whether an analyte is present at a predetermined concentration level by carrying out a subtractive reaction prior to the indicator reaction. Thereby the strip generates a predetermined response level only if the analyte is present at a predetermined concentration or more.
The patents discussed above involve xe2x80x9cwipe-offxe2x80x9d strips, in which the interference between the color of whole blood and the color developed by the indicator dye is minimized by wiping excess blood sample from the strip surface. Alternative approaches involve applying the blood sample to one surface of the strip and measuring the color on the opposite surface. The patents discussed below are examples.
U.S. Pat. No. 4,935,346, issued Jun. 19, 1990 to R. Phillips et al., discloses a meter, strip, and method for determining the glucose concentration in a sample of whole blood. The method involves simply applying a sample of whole blood to a first (xe2x80x9csamplexe2x80x9d) surface of an inert porous matrix that is impregnated with a reagent. The sample migrates toward the opposite, xe2x80x9ctestingxe2x80x9d surface, as the glucose interacts with the reagent to produce a light-absorbing reaction product. A reading of reflectance from the testing surface indicates the glucose concentration. Reflectance measurements are made at two separate wavelengths in order to eliminate interferences. A timing circuit is triggered by an initial decrease in reflectance caused by wetting of the testing surface by the sample having passed through the matrix.
U.S. Pat. No. 5,306,623, issued Apr. 26, 1994 to Kiser et al., discloses a visual blood glucose test strip that involves applying a glucose-containing whole blood sample to one side of the strip and taking the glucose reading on the opposite side, after red blood cells have been separated out and the sample has reacted with a reagent in the strip. An asymmetric polysulfone membrane was found especially useful as a single layer matrix for the strip. (See also U.S. Pat. No. 5,418,142, issued May 23, 1995 and U.S. Pat. No. 5,719,034, issued Feb. 17, 1998.)
U.S. Pat. No. 5,563,031, issued Oct. 8, 1996 to Y. S. Yu, discloses a dye couple useful in dry reagent strips for detecting analytes, such as glucose, in biological fluids. The dye couple comprises meta [3-methyl-2-benzothiazolinone hydrazone] N-sulfonyl benzenesulfonate monosodium combined with 8-anilino-1-naphthalene sulfonic acid ammonium (MBTHSB-ANS) and is used as an indicator in a reaction cascade producing a strong oxidizing agent, such as hydrogen peroxide. An advantage of the couple is that it is soluble in aqueous solution, but becomes insoluble upon oxidative coupling, thereby minimizing fading and providing a stable endpoint.
White-Stevens and Stover, Clin. Chem. 28, 589-595 (1982), discuss interference that can be caused by ascorbic acid on diagnostic tests. The ascorbic acid causes a lag time in color development of tests based on the use of peroxidase and redox indicators.
M. J. Sherwood et al., Clin. Chem. 29; 438-445 (1983) discuss a visual reagent strip for use in conjunction with a calibrated color scale. The strip uses two pads, each formulated for a different part of the normal range. The technology underlies the Visidex(trademark) reagent strip, which is visually read. Other commercially-available visual strips include Dextrostix(copyright) reagent strips, Chem-strip bG(copyright), and SinartStrip(trademark) reagent strips.
In accordance with the present invention, a visual blood glucose test strip comprises
a) a spreading layer for accepting a blood sample on a major surface and passing the sample to a second major surface, opposite;
b) an intermediate layer comprising first and second membranes, substantially side-by-side, each having a top major surface adjoining the second major surface of the spreading layer to receive a part of the blood sample and each containing a reagent that can react with glucose in the sample, as it passes through the membrane, to cause a color change in the reagent, the second membrane further comprising an inhibitor and a dye, and
c) a support layer to support the other layers and to permit any color changes in the membranes to be visible through it.
As used in this specification and the appended claims, xe2x80x9creagentxe2x80x9d refers to the components that may be on, or in, both membranes, as opposed to the inhibitor and dye, which are only on, or in, the second membrane. The dye is inert, in the sense that its color is substantially independent of the glucose concentration. Its purpose is to enhance the difference in color between the two membranes.
Among the advantages of the test strip of this invention are that it requires no wiping, can use a small blood sample, and provides results rapidly.